Drugs slow diabetes patients' kidney damage.

Two drugs prescribed for high blood pressure show signs of forestalling kidney damage in people with type 2, or adult-onset, diabetes, according to three new studies. The findings, reported in the Sept. 20 NEW ENGLAND JOURNAL OF MEDICINE, could give physicians a new way to block this dangerous complication.

High blood pressure can lead to kidney problems, particularly in people with diabetes. While scientists don't fully understand the causes of high blood pressure, they know that a hormone called angiotensin can contribute to it. Some blood pressure medications offset angiotensin's effects in much of the body, but they aren't as effective in the kidneys.

Part of the problem lies in the kidneys' unusual design. Blood enters the organs via arteries and then fans out into microscopic capillaries. There, clusters of cells called glomeruli filter out impurities, dumping them into the urine. However, the blood doesn't flow directly back into veins heading out of the kidney. Instead, it gathers in another artery and spreads into more capillaries to nourish kidney tissues before it finally exits.

Although the blood pressure medications that have been in use the longest relax the arteries entering the kidneys, they don't always act adequately in the internal kidney capillaries. A bottleneck can ensue that swamps the glomeruli with high-pressure blood and damages them, says Barry M. Brenner of Brigham and Women's Hospital in Boston.

Seeking to prevent such damage, scientists in the early 1990s began testing blood pressure drugs called angiotensin-converting enzyme (ACE) inhibitors to see if they improve kidney function. These drugs suppress the enzyme that triggers angiotensin production. They limit kidney damage, but whether they confer full protection remains unproven.

Taking yet another approach, Brenner and his colleagues gave diabetes patients losartan, a drug that occupies docking sites on cells to which angiotensin would otherwise bind.

The researchers assigned 327 diabetes patients who had high blood pressure and some kidney damage to receive either losartan or an inert pill. The patients also continued taking standard blood pressure drugs. After 3.4 years, the patients getting losartan were significantly less likely to have any of three outcomes: damaged glomeruli leading to a doubling of the compound creatinine in the urine, kidney failure, or death.

Although losartan has been on the market for several years, physicians generally prescribe it for high blood pressure, not kidney problems. "This is a novel use," Brenner says.

The other two studies examined another blood pressure drug, irbesartan, which also blocks angiotensin receptors. Edmund J. Lewis of Rush-Presbyterian-St. Luke's Medical Center in Chicago and his colleagues assigned 1,715 patients with high blood pressure to receive either a placebo, irbesartan, or a drug called amlodipine, which relaxes artery spasms. Alter nearly 3 years, the irbesartan group was only two-thirds as likely as the other groups to show doubled creatinine concentrations in their urine.

When blood can't flow through the glomeruli smoothly, scar tissue forms, leaving part of the organ damaged, Lewis says. Although losartan and irbesartan may not reverse kidney damage, they could delay by 2 or 3 years the day when a person with diabetes and kidney problems needs dialysis, he estimates.

In the third study, scientists gave irbesartan or a placebo to 590 patients with traces of albumin in their urine, a trait that's been linked to later kidney failure. After 2 years, patients receiving the larger of two dosages of irbesartan were about one-third as likely as those on placebos to develop significantly higher concentrations of albumin in their urine, a sign of kidney problems, reports study coauthor Hans-Henrik Parving of the Steno Diabetes Center in Gentofte, Denmark.

In response to these studies, regulators should consider permitting manufacturers to label the drugs as treatments for diabetes patients with high blood pressure and early signs of kidney damage, says Thomas H. Hostetter of the National Institute of Diabetes and Digestive and Kidney Diseases in Bethesda, Md.